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Urinary tract infections

Less effective drugs include all the beta lactams. This used to be the drug of choice for UTIs - ampicillin or some other kind of betalactam - perhaps a cephalosporin. They are safe and are often active against uropathogens, which is perhaps not as likely to be true as for fluoroquinolones. There are variable resistance patterns. When they are known to be effective in vitro, they still aren't quite as good as you get with a fluoroquinolone or TMP sulfa. The problem is not just that there is more resistance out there, but there is something biologically different about how they work that makes them less effective.

In my hospital, if you present with a UTI, you are admitted and guaranteed ampicillin and gentamicin; it's a ritual. It doesn't make a lot of sense, but people love it. If the person is pen-allergic, they get vancomycin and gentamicin, which is an even more mysterious combination. Now there is a whole class of drugs that have been called urinary antiseptics. Nitrofurantoin is probably the most effective of all these antiseptics and it is an interesting drug. It does seem to work against a variety of bacteria, including enterococcus, which is good to remember for the person who may be pen-allergic.

Now the next thing we will talk about is methenamine. Methenamine has been promoted for years for the treatment of urinary infections. Supposedly, the way it works is that it gets converted to formic acid and that the formic acid is generally inhibitory to microbes, including bacteria and yeast. This is the concept that people have promoted for a long time. Methenamine is a very small molecule that in an acidic environment is broken down into formic acid; the formic acid is inhibitory and therefore it works. There is one problem with that; the formic acid production is very slow. It happens at a fairly fixed rate that may take many hours for the formic acid concentration to achieve a level where it can actually kill bacteria. It may take more hours for that to happen than you spend between void A and void B of you day. So obviously, if it is happening in the toilet, that is not doing you any good; it has to happen while it is still in your bladder.

The newest thing out there is fosfomycin. This is a drug that has been around for a very long time, but it new to this country. For various reasons , it has really only been marketed for urinary infections. The way it is given is kind of unusual. You give one huge slug of it, and that is really the only way that you can officially give it - a big 3-gram dose - and you are done. You can imagine that there might be some problems if you have an infection that would require more prolonged treatment.

Duration of therapy is one of the more controversial areas. This is what my editorial was about when I first wrote my paper - it was about one-day therapy. Those of you who have long memories may remember back to when miniskirts were popular for the first time. Remember that we used to use a very long course of therapy for UTIs - two weeks was a sort of down payment and you would go up from there. Then some people noticed that their patients were getting better the next day, so they tried using a week, then they tried just using three days, then they tried just using two doses in one day and then pretty soon it was like the limbo contest - how low can you go - one double strength a day, one single strength, half a single strength. So we had this era of ever decreasing dosing for UTIs. It got to the point where we weren't really reducing the drug side effects anymore, because the drugs had so few side effects at these very low doses that it was a kind of game. Initially, it looked like it was pretty good treatment. There were a fair amount of relapses.

For the more severe infections, particularly those involving the kidneys, we like to use a bit longer course. Why is that? Well, it turns out that even infections involving the kidneys can respond to a three-day course of therapy and you can have some cures. But you do have a larger number of relapses. So I think that when you are quite certain about kidney involvement, you really want to use a longer course.

We know that three-day courses are okay for uncomplicated infections. The short courses are great and TMP sulfa and quinolones really are better than nitrofurantoin and better than beta lactams. Beta lactams are particularly not great for any problems where there is a recurrence issue, because they don't do anything good about that.

Now let's talk about this patient. This is a young woman who has a bicoastal relationship with her husband. She lives in Philadelphia, he lives in L.A., but they get together about every three or four weeks. This is not so rare anymore - people have a lot of frequent flyer miles and they can go back and forth. They decided that rather than taking the pill and worrying about all the side effects of the pill, since they only have sex every three or four weeks, they will just use a diaphragm and a spermicide. She was starting to notice that about every other time they got together, she would have a UTI, so she wasn't looking forward to.

People have talked about diaphragms and spermicides. Each of them are independent risks. In other words, if you use a diaphragm you have risk A and if you use a spermicide you have risk B; if you use them both, you have risk A plus B. The bigger risk of the two is the spermicide. We used to think it was the diaphragm because of its shape compressing the urethra, but the bigger risk is the spermicide. Spermicide alters the content of the vaginal flora. In Africa they have done some studies looking at spermicides as HIV preventive agents. The results were very sobering. The actual conversion rate was higher in the women.